Journal Article Annotations
2023, 3rd Quarter

Pain

Annotations by Alissa Hutto, MD, Julian Raffoul, MD
October, 2023

Trazodone for sleep disturbance in opioid dependent patients maintained on buprenorphine: A double blind, placebo-controlled trial.

PUBLICATION #1 — Pain

Trazodone for sleep disturbance in opioid dependent patients maintained on buprenorphine: A double blind, placebo-controlled trial.

Piyush Goyal, Dheeraj Kattula, Ravindra Rao, Roshan Bhad, Ashwani Kumar Mishra, Anju Dhawan.

Abstract: Drug Alcohol Depend. 2023 Sep 1:250:110891. doi: 10.1016/j.drugalcdep.2023.110891. Epub 2023 Jul 8.

Background:
Sleep disturbances are seen even in individuals on opioid agonist treatment (OAT). Established pharmacotherapy for sleep disturbances such as benzodiazepines have misuse potential and increased mortality risk in patients with OAT. No study has explored the role of trazodone on sleep disturbance in individuals maintained on buprenorphine. We aimed to assess the efficacy of trazodone in improving sleep disturbance among individuals maintained on buprenorphine.

Methods:
The study was a double-blind, placebo-controlled, parallel, randomised trial. Adult males (18-60 years) stabilised on buprenorphine with Pittsburgh Sleep Quality Index (PSQI) score of above five, without other psychiatric comorbidity were randomised to receive either trazodone (50-150mg per day) or placebo. Sleep-50 questionnaire, Epworth Sleepiness Scale (ESS), Brief Pain Inventory (BPI), Clinical Opiate Withdrawal Scale (COWS), Depression, Anxiety and Stress Scale (DASS)-21, Visual Analogue Scale (VAS) for opioid craving, and PSQI were assessed at baseline and at the end of six weeks.

Results:
Fifty-one patients were allocated to trazodone arm and 49 to placebo arm. Side-effects of trazodone were minimal and well-tolerated with comparable discontinuation rates between both groups. Significantly greater proportion of patients on trazodone (82%, mean dose 101.9 mg) had PSQI scores five or less than those on placebo (16%) at the end of six weeks. Sleep improvement was in various components like sleep quality, latency, efficiency, and duration of sleep.

Conclusion:
Trazodone is well-tolerated and effective in improving sleep disturbances in individuals with opioid dependence maintained on buprenorphine over a six-week period.

Annotation

The finding:
This double-blind randomized control study found that for patients with opioid use disorder treated with buprenorphine, trazodone was more effective for improving sleep disturbance than placebo. Sleep quality was assessed by a self-report scale (PSQI) at six weeks of treatment, and the average trazodone dose reached in the study was 101mg (starting at 50mg and patients could self-titrate up to 150mg).

Strength and weaknesses:
The study had an thoughtful design with attention tomany confounding factors including withdrawal symptoms and changes in pain scores during treatment. They did not exclude all substance use (allowed nicotine, and non-high-risk cannabis and alcohol use), which is a strength for real-world application of these results. The structure of the buprenorphine clinic allowed weekly dispensing with patient-directed flexibility. One limitation included the imbalance of biological sex in the study, which only included. However, a bigger weakness was the exclusion of patients on psychotropic medications and/or with a comorbid psychiatric disorder aside from a sleep disorder, and those on psychotropic medications. This exclusion brought the available patient pool down by more than 50% and limits generalizability of the results. Another limitation was the short follow-upperiod, with no evidence that improved sleep can be maintained over the long term.

Relevance:
Despite the narrow range of patients included in this study, the authors demonstrated that trazodone may be effective for sleep in patients with opioid use disorder on buprenorphine and have minimal side effects. The study may also help C-L psychiatrists direct discussions about another trazodone trial for patients who may not have had success with trazodone while on full opioid agonists or on methadone but who are now on buprenorphine.